INCREASED APOPTOSIS OF IMMUNOREACTIVE HOST CELLS AND AUGMENTED DONOR LEUKOCYTE CHIMERISM NOT SUSTAINED INHIBITION OF B7 MOLECULE EXPRESSION ARE ASSOCIATED WITH PROLONGED CARDIAC ALLOGRAFT SURVIVAL IN MICE PRECONDITIONED WITH IMMATURE DONOR DENDRITIC CELLS PLUS ANTI-CD40L mAb

摘要

BackgroundWe previously reported the association among donor leukocyte chimerism, apoptosis of presumedly IL-2-deficient graft-infiltrating host cells, and the spontaneous donor-specific tolerance induced by liver but not heart allografts in mice. Survival of the rejection-prone heart allografts in the same strain combination is modestly prolonged by the pretransplant infusion of immature, costimulatory molecule (CM) deficient donor dendritic cells (DC), an effect that is markedly potentiated by concomitant CM blockade with anti-CD40L (CD154) monoclonal antibody (mAb). We investigated whether the long survival of the heart allografts in the pretreated mice was associated with donor leukocyte chimerism and apoptosis of graft-infiltrating cells, if these end points were similar to those in the spontaneously tolerant liver transplant model, and whether the pretreatment effect was dependent on sustained inhibition of CM expression of the infused immature donor DC. In addition, apoptosis was assessed in the host spleen and lymph nodes, a critical determination not reported in previous studies of either spontaneous or “treatment-aided” organ tolerance models.